Exposure to oxygen and reactive oxygen species (hydroxyl radical, superoxide, hydrogen peroxide, and the like) permits the oxidation of sensitive sites on protein molecules. Of sensitive sites, the sulfur of methionine is particularly subject to attack. The enzyme, methionine sulfoxide reductase, can reduce oxidized methionine and thereby repair some of the damage. We have previously shown the wide distribution of the enzymic activity in nature. The peptide-linked methionine sulfoxide can be reduced at the expense of dithiothreitol in routine assays, or NADPH can provide the reducing power via thioredoxin and thioredoxin reductase. In addition to the chiral center at the carbon, an additional center is generated at the sulfur when methionine sulfoxide is formed. Methionine sulfoxide reductase utilizes only the "s" form of the sulfoxide as substrate, not the "r" form. This specificity appears to apply to the enzyme from Saccharomyces cerevisiae and to that from Escherichia coli. It is probable that the specificity is a general property of such enzymes. Yeast cells in which the reductase has been eliminated are less able to withstand oxidative stress (such as exposure to hydrogen peroxide) than are wild-type cells. Cells which contain multiple copies of the gene for the reductase grow much like the wild-type cells.